Oliveira Felipe P de, Nogueira Mateus L, Galvão Alexandre F C, Dias Rosane B, Bezerra Daniel P
Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia 40296-710, Brazil.
Department of Biological Sciences, State University of Feira de Santana, Feira de Santana, Bahia 44036-900, Brazil.
Mol Ther Oncol. 2025 Jun 13;33(3):201008. doi: 10.1016/j.omton.2025.201008. eCollection 2025 Sep 18.
Triple-negative breast cancer (TNBC) is defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is unresponsive to targeted therapy and is associated with a high degree of malignancy, a high propensity for metastasis, high recurrence rates, and poor prognosis. In the modern concept of cancer biology, a subset of cancer cells known as tumor-initiating cells or cancer stem cells (CSCs) are defined as essential for the development and dissemination of cancer. These are a population of highly tumorigenic and self-renewing pluripotent cells that are inherently associated to the initiation, dissemination, relapse, and development of drug resistance. Specifically, some cell signaling pathways may affect the ability of CSCs to self-renew, differentiate, proliferate, and survive. To guide future research, in this review, we address compounds that target cell signaling and eliminate TNBC stem cells. Potential translational inhibitors of the Hedgehog, nuclear factor κB (NF-κB), Wnt, Notch, Hippo, TGF-β, JAK/STAT, and PI3K/AKT/mTOR cell signaling pathways are discussed, with a focus on TNBC stem cell eradication.
三阴性乳腺癌（TNBC）的定义是缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达。它对靶向治疗无反应，并且与高度恶性、高转移倾向、高复发率和不良预后相关。在现代癌症生物学概念中，一种被称为肿瘤起始细胞或癌症干细胞（CSCs）的癌细胞亚群被定义为癌症发生和扩散所必需的。这些是一群具有高度致瘤性和自我更新能力的多能细胞，它们与肿瘤的起始、扩散、复发和耐药性的发展内在相关。具体而言，一些细胞信号通路可能会影响癌症干细胞的自我更新、分化、增殖和存活能力。为指导未来的研究，在本综述中，我们探讨了靶向细胞信号并消除TNBC干细胞的化合物。讨论了Hedgehog、核因子κB（NF-κB）、Wnt、Notch、Hippo、TGF-β、JAK/STAT和PI3K/AKT/mTOR细胞信号通路的潜在翻译抑制剂，重点是根除TNBC干细胞。
